A comprehensive review on microbial production of vanillin: metabolic engineering strategies and pathway-specific yields across microbial hosts.

Vanillin is one of the chief flavors used in the food, beverage, fragrance, and medicinal industries. It is a phenolic aldehyde with aldehyde, ethers, and hydroxyl as functional groups and is chemically known as 4-hydroxy-3-methoxybenzaldehyde, obtained from species like Vanilla planifolia, Vanilla tahitensis, and Vanilla pompona. The Food and Drug Administration (FDA) and the Flavor and Extract Manufacturers Association (FEMA) have recommended vanillin as a safe flavor additive for consumption. The international vanillin market has experienced noteworthy growth in the past few years, recording a CAGR of 7% from 2018 to 2022. It is forecasted to expand at a 9.3% CAGR by the end of 2033. Vanillin can be biologically produced in three ways: microbial vanillin production, Enzyme-mediated vanillin production, and plant-based method. Among several methods, microbial bioconversion methods replicate vanillin production similar to that of natural vanilla plants, with the major advantage of using inexpensive agricultural by-products, such as lignin and ferulic acid, as substrates to produce vanillin under optimized conditions. This review presents a summary of different metabolic pathways followed by bacteria, fungi, yeast, and recombinant strains in the biological way of producing vanillin and highlights the mechanism of each pathway, including beta-oxidative deacetylation, non-beta oxidative deacetylation, and side reduction paths, with the intermediates and the enzymes taking part in each step. This review also highlights the yield of vanillin production using different substrates by specific species to date. The conclusion section describes vanillin production by biotechnological methods with recombinant cells to increase yield and its future scope.